Determinación de una técnica de referencia para la susceptibilidad antimicrobiana de bacterias anaeróbicas de importancia clínica

The selection of antibiotics for the treatment of anaerobic infections is generally based on purely empirical criteria, with antimicrobial sensitivity tests being carried out only in reference centres. For this reason, it is important to investigate a technique appropnate for use in less specialized clinical bacteriology laboratories. In this study, four antimicrobial sensitivity tests (elution in a broth disk, macrodilution, rnicrodilution and dilution in agar) were carried out using four reference strains with known sensitivity patterns. The reproducibility, concordance, speed and ease of use of each test was compared. The results obtained showed that the most reproducibletest was dilution in agar, followed by microdilution, macrodilution and elution. In terms of concordance the best test was dilution in agar, followed by macrodilution, elution and microdilution. The most complex test was dilution in agar, followed by microdilution, macrodilution and elution. As this study did not find any single test which, aione, proved better than any other in all the criteria analized, we recommend that a combination of at least two tests be used in the study of antimicrobial susceptibility of anaerobes.La selección de antibióticos para el tratamiento de infecciones por microorganismos anaeróbicos se hace en forma empírica en la mayoría de los casos; por tanto, el empleo de técnicas para determinar la susceptibilidad antimicrobiana es controvertido y sólo se realiza en centros de referencia. Con la aparición de cepas resistentes a los antimicrobianos de elección, es necesario determinar entre las técnicas estandarizadas una que pueda ser realizada en un laboratorio con cierta infraestructura para el trabajo en bacteriología clínica. Se realizaron cuatro pruebas estandarizadas por el NCCLS: elución de disco en caldo, macrodilución, microdilución y dilución en agar, empleando cuatro cepas de referencia. Los datos obtenidos fueron analizados para determinar la reproducibilidad, la concordancia y la complejidad de las pruebas. Empleando los criterios analizados, se obtuvo en orden descendente: en reproducibilidad, la dilución en agar, microdilución, macrodilución y elución; en concordancia. la dilución en agar, macrodilución, elución y microdilución; y en complejidad, dilución en agar, microdilución, macrodilución y elución. Debido a la variedad de los resultados obtenidos no se pudo recomendar una sola técnica para la determinación de la susceptibilidad de microorganismos anaeróbicos de importancia clínica; en algunos casos y teniendo en cuenta el microorganismo y el antibiótico a probar, la realización de por lo menos dos de ellas permitiría esa determinación

The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF. A total of 1,071 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded. Three groups of patients were identified. Pre-ACLF patients (n = 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n = 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC). Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge. ClinicalTrials.gov number: NCT03056612. Lay summary: Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death - termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD - patients in this group rarely require hospital admission and have a much lower 1-year mortality risk

PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

Background & Aims: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (ADNo ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes. Methods: The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome. Results: Among various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality. Conclusions: This study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis. Lay summary: Acute decompensation (AD) of cirrhosis is characterized by a rapid deterioration in patient health. Herein, we aimed to analyze the precipitating events that cause AD in patients with cirrhosis. Proven bacterial infections and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96-97%) cases of AD and acute-on-chronic liver failure. Whilst the type of precipitant was not associated with mortality, the number of precipitant(s) was. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD. Specific preventive and therapeutic strategies targeting these events may improve patient outcomes. (c) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Determinación de una técnica de referencia para la susceptibilidad antimicrobiana de bacterias anaeróbicas de importancia clínica

La selección de antibióticos para el tratamiento de infecciones por microorganismos anaeróbicos se hace en forma empírica en la mayoría de los casos; por tanto, el empleo de técnicas para determinar la susceptibilidad antimicrobiana es controvertido y sólo se realiza en centros de referencia. Con la aparición de cepas resistentes a los antimicrobianos de elección, es necesario determinar entre las técnicas estandarizadas una que pueda ser realizada en un laboratorio con cierta infraestructura para el trabajo en bacteriología clínica. Se realizaron cuatro pruebas estandarizadas por el NCCLS: elución de disco en caldo, macrodilución, microdilución y dilución en agar, empleando cuatro cepas de referencia. Los datos obtenidos fueron analizados para determinar la reproducibilidad, la concordancia y la complejidad de las pruebas. Empleando los criterios analizados, se obtuvo en orden descendente: en reproducibilidad, la dilución en agar, microdilución, macrodilución y elución; en concordancia. la dilución en agar, macrodilución, elución y microdilución; y en complejidad, dilución en agar, microdilución, macrodilución y elución. Debido a la variedad de los resultados obtenidos no se pudo recomendar una sola técnica para la determinación de la susceptibilidad de microorganismos anaeróbicos de importancia clínica; en algunos casos y teniendo en cuenta el microorganismo y el antibiótico a probar, la realización de por lo menos dos de ellas permitiría esa determinación